Prospective study to define the clinical utility and benefit of Decipher testing in men following prostatectomy

Abstract

Background Genomic classifiers (GC) have been shown to improve risk stratification post prostatectomy. However, their clinical benefit has not been prospectively demonstrated. We sought to determine the impact of GC testing on postoperative management in men with prostate cancer post prostatectomy. Methods Two prospective registries of prostate cancer patients treated between 2014 and 2019 were included. All men underwent Decipher tumor testing for adverse features post prostatectomy (Decipher Biosciences, San Diego, CA). The clinical utility cohort, which measured the change in treatment decision-making, captured pre-and postgenomic treatment recommendations from urologists across diverse practice settings (n = 3455). The clinical benefit cohort, which examined the difference in outcome, was from a single academic institution whose tumor board predefined "best practices" based on GC results (n = 135). Results In the clinical utility cohort, providers' recommendations pregenomic testing were primarily observation (69%). GC testing changed recommendations for 39% of patients, translating to a number needed to test of 3 to change one treatment decision. In the clinical benefit cohort, 61% of patients had genomic high-risk tumors; those who received the recommended adjuvant radiation therapy (ART) had 2-year PSA recurrence of 3 vs. 25% for those who did not (HR 0.1 [95% CI 0.0-0.6], p = 0.013). For the genomic low/intermediate-risk patients, 93% followed recommendations for observation, with similar 2year PSA recurrence rates compared with those who received ART (p = 0.93). Conclusions The use of GC substantially altered treatment decision-making, with a number needed to test of only 3. Implementing best practices to routinely recommend ART for genomic-high patients led to larger than expected improvements in early biochemical endpoints, without jeopardizing outcomes for genomic-low/intermediate-risk patients.

Clinical Applications of Molecular Biomarkers in Prostate Cancer

“…Decipher was first validated in patients who underwent radical prostatectomy. The test results provide an estimate of the risk of developing metastatic progression in patients whose surgical specimen presents unfavourable characteristics (stage pT3 and/or positive margins) [79][80][81][82]. These initial findings were supported by subsequent studies that included postoperative radiotherapy (PORT) [83].…”

“…In a similar study, Marascio et al [79] prospectively assessed the impact of Decipher in the postoperative setting in terms of clinical benefit (135 patients) and clinical utility (n = 3455). Clinical utility was quantified in terms of a change in the recommended treatment (39% of patients), with only three tests needed to change one treatment decision.…”

Incorporating Prognostic Biomarkers into Risk Assessment Models and TNM Staging for Prostate Cancer

“…Moreover, Spratt et al has developed an internally validated integrated clinical-genomic risk group stratification for localized prostate cancer that outperforms traditional NCCN risk classification [56]. In addition, prospective trials confer that genomic testing post RP confers both decreased patient-related anxiety and improved decision making [57,58]. Subsequently, a defined role of genomic testing after RP has been included in the most recent NCCN guidelines [6].…”

Молекулярно-Генетические Маркеры В Прогнозировании И лечении Рака Простаты

“…Целью было определить влияние результата теста Decipher на клиническое решение, которое впоследствии было изменено у 32% пациентов. В аналогичном исследовании Marascio et al [78] проспективно оценили влияние Decipher в послеоперационном периоде с точки зрения клинической пользы (135 пациентов) и клинической применимости (n = 3455). Клиническая польза была количественно оценена с точки зрения изменения рекомендованного лечения (39% пациентов), при этом для изменения одного решения о лечении потребовалось всего три теста.…”